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Hepatic Response to the Interaction Between Thymoquinone and Iron-Dextran: an In Vitro and In Vivo Study

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Abstract

Iron is one of the most important essential elements for cell function. However, iron overload can exert destructive effects on various tissues, especially the liver. The present study was designed to evaluate the effect of thymoquinone (TQ) on hepatotoxicity induced by iron-overload in in vitro and mouse model. After in vitro studies, thirty mice were divided into five groups, six each. Group 1 received normal saline. Group 2 received five doses of iron dextran (i.p; 100 mg/kg, one dose every 2 days). Group 3 received TQ (orally, 2 mg/kg/day). Groups 4 and 5 were administrated iron dextran saline (i.p; 100 mg/kg, one dose every 2 days) following treatment with 0.5 and 2 mg/kg/day of TQ, respectively. Based on the findings of the DPPH experiment, although TQ has significant anti-radical potential, at a safe dose of 15 × 10+3 nM, it reduced the IC50 of iron dextran on HepG2 cells by about 25%, in in vitro. Following administration of low-dose TQ (0.5 mg/kg), a significant improvement was observed in serum hepatic enzymes activity and hepatic lipid peroxidation compared to iron dextran. However, administration of TQ-high dose (2 mg/kg) led to decrease antioxidant defense alongside increased serum hepatic enzymes and pathological damages in iron dextran–treated animals. Due to the different efficacy of TQ in treatment groups, it seems that the TQ therapeutic index is low and does not have significant safety in the iron overload status.

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Funding

The financial support for conducting the research project “Evaluation of biochemical and histological effects of thymoquinone on iron-induced toxicity in male mice” was provided by the Vice-Chancellor of Research and Technology, Hamadan University of Medical Sciences, Hamadan, I.R. Iran (Grant No. 140003181967).

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Authors and Affiliations

  1. Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Farzad Ghasemi, Fatemeh Ghaffari & Amir Nili-Ahmadabadi

  2. Faculty of Pharmacy, Eastern Mediterranean University, 99628, Via Mersin 10, Famagusta, North Cyprus, Turkey

    Farzad Ghasemi

  3. Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran

    Fatemeh Ghaffari & Amir Nili-Ahmadabadi

  4. Medical Education Research Center, Department of Pathology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

    Navid Omidifar

  5. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Masoumeh Taheri Azandaryani

Authors
  1. Farzad Ghasemi
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  2. Fatemeh Ghaffari
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  3. Navid Omidifar
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  4. Masoumeh Taheri Azandaryani
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  5. Amir Nili-Ahmadabadi
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Contributions

Farzad Ghasemi helped in the bibliography, biochemical analysis, and did the work and drafted the manuscript as his Pharm. D thesis. Fatemeh Ghaffari contributed in performing in vitro studies. Navid Omidifar assisted in doing histopathological analyses. Masoumeh Taheri Azandaryani contributed in animal laparotomy surgery. Amir Nili-Ahmadabadi conceived and supervised the study and edited the manuscript and has been the supervisor of the thesis.

Corresponding author

Correspondence to Amir Nili-Ahmadabadi.

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Ethics Approval

The study was conducted based on the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Hamadan University of Medical Sciences (approval number: IR.UMSHA.REC.1400.098).

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The authors declare no competing interests.

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Ghasemi, F., Ghaffari, F., Omidifar, N. et al. Hepatic Response to the Interaction Between Thymoquinone and Iron-Dextran: an In Vitro and In Vivo Study. Biol Trace Elem Res 201, 1358–1367 (2023). https://doi.org/10.1007/s12011-022-03249-9

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